{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:18:04Z","timestamp":1778732284887,"version":"3.51.4"},"reference-count":13,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We describe three patients from three unrelated consanguineous families, all homozygous for the c.301C&amp;gt;T (p.Arg101Trp) variant in the iodotyrosine deiodinase (IYD) gene. These patients presented in late childhood around puberty with diffuse goiter, primary hypothyroidism, and negative thyroid autoantibodies, consistent with thyroid dyshormonogenesis (DH). Initiation of levothyroxine therapy led to a significant reduction in goiter size and clinical improvement. Notably, all patients had normal thyroid function at neonatal screening, suggesting a delayed clinical manifestation of congenital hypothyroidism. These cases highlight the importance of considering genetic causes of hypothyroidism, particularly in consanguineous families. The ultrasound findings of a homogeneously enlarged, hypervascularized goiter without micronodularity in adolescent patients with non-autoimmune hypothyroidism should prompt consideration of DH, specifically IYD variants. Increased clinical awareness, combined with targeted molecular testing once an index patient is identified, can facilitate detection of the pathogenic variant, timely initiation of treatment, and screening of at-risk family members.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag111","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:44:58Z","timestamp":1775043898000},"source":"Crossref","is-referenced-by-count":0,"title":["Thyroid dyshormonogenesis caused by iodotyrosine deiodinase pathogenic variant: three cases presenting in adolescence"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-7056","authenticated-orcid":false,"given":"Isabelle En Xin","family":"Choong","sequence":"first","affiliation":[{"name":"Developmental Endocrinology Research Group, University of Glasgow , Glasgow G12 8QQ ,","place":["UK"]},{"name":"Department of Paediatric Endocrinology, Royal Hospital for Children , Glasgow G51 4TF ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-6360","authenticated-orcid":false,"given":"Suet Ching","family":"Chen","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Research Group, University of Glasgow , Glasgow G12 8QQ ,","place":["UK"]},{"name":"Department of Paediatric Endocrinology, Royal Hospital for Children , Glasgow G51 4TF ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2316-3334","authenticated-orcid":false,"given":"Mohamad Guftar","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Research Group, University of Glasgow , Glasgow G12 8QQ ,","place":["UK"]},{"name":"Department of Paediatric Endocrinology, Royal Hospital for Children , Glasgow G51 4TF ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"issue":"2","key":"2026051323532937800_luag111-B1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s42000-020-00267-x","article-title":"Genetics of primary congenital hypothyroidism\u2014a review","volume":"20","author":"Kostopoulou","year":"2021","journal-title":"Hormones (Athens)"},{"issue":"2","key":"2026051323532937800_luag111-B2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/ped4.12324","article-title":"Genetics of congenital hypothyroidism: modern concepts","volume":"6","author":"Stoupa","year":"2022","journal-title":"Pediatr Investig"},{"issue":"4","key":"2026051323532937800_luag111-B3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.beem.2018.05.002","article-title":"Genetics and management of congenital hypothyroidism","volume":"32","author":"Persani","year":"2018","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"2","key":"2026051323532937800_luag111-B4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.beem.2017.03.006","article-title":"Iodide handling disorders (NIS, TPO, TG, IYD)","volume":"31","author":"Targovnik","year":"2017","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"2","key":"2026051323532937800_luag111-B5","doi-asserted-by":"crossref","first-page":"e240348","DOI":"10.1530\/ETJ-24-0348","article-title":"Genetics of primary congenital hypothyroidism: three decades of discoveries and persisting etiological challenges","volume":"14","author":"Stoupa","year":"2025","journal-title":"Eur Thyroid J"},{"issue":"4","key":"2026051323532937800_luag111-B6","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1097\/MOP.0b013e32834726a4","article-title":"Genetic causes of congenital hypothyroidism due to dyshormonogenesis","volume":"23","author":"Grasberger","year":"2011","journal-title":"Curr Opin Pediatr"},{"issue":"17","key":"2026051323532937800_luag111-B7","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1056\/NEJMoa0706819","article-title":"Mutations in the iodotyrosine deiodinase gene and hypothyroidism","volume":"358","author":"Moreno","year":"2008","journal-title":"N Engl J Med"},{"key":"2026051323532937800_luag111-B8","author":"McKusick"},{"issue":"4","key":"2026051323532937800_luag111-B9","doi-asserted-by":"crossref","first-page":"814","DOI":"10.3390\/nu15040814","article-title":"Optimizing Growth: The Case For Iodine","volume":"15","author":"Rigutto-Farebrother","year":"2023","journal-title":"Nutrients"},{"issue":"2","key":"2026051323532937800_luag111-B10","doi-asserted-by":"crossref","first-page":"K5","DOI":"10.1093\/ejendo\/lvae100","article-title":"Hypothyroidism due to biallelic variants in IYD: description of 4 families and a novel variant","volume":"191","author":"Boros","year":"2024","journal-title":"Eur J Endocrinol"},{"issue":"10","key":"2026051323532937800_luag111-B11","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1210\/jcem-15-10-1216","article-title":"The occurrence of mono- and di-iodotyrosine in the blood of a patient with congenital goiter","volume":"15","author":"Stanbury","year":"1955","journal-title":"J Clin Endocrinol Metab"},{"issue":"17","key":"2026051323532937800_luag111-B12","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1056\/NEJMe0802188","article-title":"Reduce, Recycle, Reuse\u2014iodotyrosine deiodinase in thyroid iodide metabolism","volume":"358","author":"Kopp","year":"2008","journal-title":"N Engl J Med"},{"issue":"1","key":"2026051323532937800_luag111-B13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/ajum.12001","article-title":"Sonography of diffuse thyroid disease","volume":"19","author":"Yuen","year":"2016","journal-title":"Australas J Ultrasound Med"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/6\/luag111\/68282499\/luag111.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/6\/luag111\/68282499\/luag111.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T03:53:42Z","timestamp":1778730822000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luag111\/8677843"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":13,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,4,29]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luag111","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,4,29]]},"article-number":"luag111"}}